Eberlin reaction

Polar acetalization and transacetalization in the gas phase to form cyclic acetals (the Eberlin reaction) 06CRV188. 

Sparrapan, R., Eberlin, L.S., Haddad, R., Cooks, R.G., Eberlin, MJ4., August , R. (2006) Ambient Eberlin Reactions via Desorption Electrospray Ionization Mass Spectrometry. J. Mass Spectrom. 41 1242-1246. 

An early example of an ion/molecule reaction carried out in an atmospheric-pressure capillary inlet reactor based on an ESI interface to a quadrupole mass spectrometer involved the study of proton transfer between amines and multiply protonated proteins by Smith (333, 334]. Smith also observed protonated adenosine 5 -monophosphate (AMP) as the product of charge inversion in the reaction of [AMP-H] with multiplyatmospheric pressure 335j. In addition, the formation of TNT Meisenheimer complex (336) and the interaction between piperidine and multiply-charged lysozyme ions generated by electrosonic spray ionization (ESSI) [337] under atmospheric pressure has been reported. Eberlin reactions (i.e., the gas-phase transacetalization reaction) of acylium ions have also been observed to occur at atmospheric pressure under in-source ion/molecule reaction conditions [338]. 

Scheme 1. Ionic transacetalization (EberUn reaction) in the gas phase under high vacuum and at atmospheric pressure. (Adapted from Cooks, R. G. Chen, H. Eberlin, M. N. Zheng, X. Tao, W. A. Polar acetaUzation and transacetalization in the gas phase The Eberlin reaction. Chem. Rev. 2006, 106, 188-211.)...

De Souza R, da Penha ET, Milagre HMS, Garden SJ, Esteves PM, Eberlin MN, Antunes OAC (2009) The three-component Biginelli reaction a combined experimental and theoretical mechanistic investigation. Chem Eur J 15 9799-9804... 

Eberlin and Cooks578 discovered that acylium ions react with neutral isoprene and other 1,3-dienes in the gas phase to form covalently bound adducts by polar [4 + 2+] Diels-alder cycloadditions. The general reaction is given in Scheme 18, where R may range from H and alkyl to unsaturated, aromatic and polar substituents. The formation... 

Eberlin also studied the Heck reaction of aryltellurides [45] and Svennebring [19] reported the identification of three types of cationic, catalytic intermediates (Fig. 4A-C) in the microwave-assisted, phosphine-containing Heck arylation of electron rich olefins. In the latter case the authors support a Pd(0)/Pd(II) cycle as opposed to a Pd(II)/Pd(IV) cycle based on ESI-MS evidence for reduction of the palladium(II) precatalyst to Pd(0) by the ligand, and oxidative addition of the aryl substrate to a Pd(0) species. None of the expected Pd-bound olefin intermediates were observed however, this is often the case either because the olefin-bound species is neutral or because OA (oxidative addition) is the turnover-limiting step and the subsequent steps occur too quickly to be observed by the sampling method (in this case sampling included quenching and dilution of samples from a reaction vessel). 

The reaction of an aryl diazonium halide with an aliphatic unsaturated compound to yield an a-halo-P-phenyl alkene and alkanes. The reaction is performed in the presence of cupric ious. The presence of an electron-withdrawing group is useful in promoting the reactivity of the alkene. See Kochi, J.K., The Meerwein reaction. Catalysis by cuprous chloride, J. Am. Chem. Soc. 11, 5090, 1955 Morales, L.A. and Eberlin, M.N., The gas-phase Meerwein reaction, Chemistry 6, 897-905, 2000 Riter, L.S., Meurer, E.C., Handberg, E.S. et al, lon/molecule reactions performed in a miniature cylindrical ion trap mass spectrometer. Analyst 128, 1112-1118, 2003 Meurer, E.C., Chen, H., Riter, E.S. et al., Meerwein reaction of phosphonium ions with epoxides and thioepoxides in the gas phase, J. Am. Soc. Mass Spectrom. 15, 398 05, 2004 Meurer, E.C. and Eberlin, M.N., The atmospheric pressure Meerwein reaction, J. Mass Spectrom. 41, 470-476, 2006. 

Meurer and Eberlin reported that the Meerwein reaction (Scheme 14) occurs efficiently at atmospheric pressure in a mass spectrometer in electrospray ionization (ESI) and chemical ionization experiments <2006JMP470>. The technique permits the analysis of high molecular weight thiiranes whose volatility is too low to fill the chamber under normal vacuum conditions. The acylium ion used was Mc2NCO, formed from the dopant tetramethylurea. An earlier study on the Meerwein reaction in a mass spectrometer was reported <2004JAM398>. 

Meurer, E. C., Santos, L. S., Pilli, R. A., Eberlin, M. N. Probing the Mechanism of the Petasis Olefination Reaction by Atmospheric Pressure Chemical Ionization Mass and Tandem Mass Spectrometry. Org. Lett. 2003, 5, 1391-1394. 

Recently, Eberlin and coworkers130 proposed an EI-MS/MS approach for the direct structural assignment of ortho- and metal para-substituted acyl and amidyl anilines in general (as well as phenols). The approach is based on the assertion that most compounds of this class should produce upon El the respective aminoacylium ion (Scheme 39), and that these diagnostic ions (and hence the position of the ring substituents) could be distinguished via selective ion/molecule reactions. 

To investigate the MBH mechanism, Coelho and Eberlin et al. have also used electrospray ionization mass spectrometry [ESI-MS/MS)] to characterize key MBH reaction intermediates. Using ESI-MS-(/MS), they also shed light on the co-catalytic role of ionic liquids in MBH reactions. Stimulated by the... 

M. N. Eberlin, Triple-stage pentaquadrupole (QqQqQ) mass spectrometry and ion/molecule reactions. Mass Spectrom. Rev. 16, 113-144 (1997). 

Eberlin, M.N. (2007) Electrospray Ionization Mass Spectrometry A Major Tool to Investigate Reaction Mechanisms in Both Solution and the Gas Phase. Eur. J. Mass Spectrom. 13 19-28. 

Sabino, A.A., Machado, A.H.L., Correia, C.R.D., Eberlin, M.N. (2004) Probing the Mechanism of the Heck Reaction with Arene Diazonium Salts by Electrospray Mass and Tandem Mass Spectrometry. Angew. Chem. Int. Ed. 43 2514-2518. 

Oliveira, F.F.D., dos Santos, M.R., Lalli, P.M., Schmidt, E.M., Bakuzis, R, Lapis, A.A.M., Monteiro, A.L., Eberlin, M.N., Neto, B.A.D. (2011) Charge-tagged Acetate Ligands As Mass Spectrometry Probes for Metal Complexes Investigations Applications in Suzuki and Heck Phosphine-free Reactions. J. Org. Chem. 76 10140-10147. 

Eberlin, M.N., Neto, B.A.D. (2014) Phosphine-free Heck Reaction Mechanistic Insights and Catalysis On Water Using a Charge-tagged Palladium Complex. New J. Chem. 38 2958-2963. 

Using ESI-MS in both the positive and negative ion modes, Eberlin and coworkers [6] monitored on-line a few MBH reactions. The proposed intermediates for the catalytic cycle of the MBH reaction (1-7, Scheme 3.3) were for the first time successfully intercepted and structurally characterized. 

By using competitive experiments, the relative efficiency of different co-catalysts wasdeterminedtobeBMICF3C02>BMI BF4>BMIPFG, which was the opposite of that observed by Afonso ef al. [8] in solution. Based on the interception of these unprecedented supramolecular species, Eberlin and coworkers propose (Scheme 3.4) that 1,3-dialkylimidazolium ionic liquids function as efficient co-catalysts for the MBH reaction by (i) activating the aldehyde toward nucleophilic attack by BMI coordination (species 8 ) and (ii) stabilizing the zwitterionic species that act as the main MBH intermediates through supramolecular coordination (species 9", lO, 11 +, and 13 + ). 

Eberlin and coworkers, [43] performed a ESI( + )-MS(/MS) investigation in which key Pd intermediates involved in the major steps of a real catalytic cyde of a Stille reaction were detected. The well-known working-model mechanism of the Stille [44]... 

Probing the mechanisms of nonmetal-catalyzed reactions by ESI-MS/MS have also been carried out by chemists. Eberlin and coworkers have described the use of ESI-MS for the interception and characterization of the organocatalytic intermediates in the DABCO-catalyzed Baylis-Hillman reaction (Scheme 4.5) [19]. Through the ESI-MS study, most proposed intermediates were successfully intercepted and characterized as protonated species, which provided strong evidence for the currently accepted catalytic cycle. In addition, the Baylis-Hillman reaction catalyzed by Lewis adds [20] and dissolved in ionic liquids [21] has also been investigated by Eberlin and coworkers. 

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